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全面转录组挖掘鉴定了晚发型子痫前期的基因表达特征和差异调控途径。

Comprehensive transcriptome mining identified the gene expression signature and differentially regulated pathways of the late-onset preeclampsia.

机构信息

Department of Medical Genetics and Molecular Biology, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran.

Department of Medical Immunology, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

出版信息

Pregnancy Hypertens. 2021 Aug;25:91-102. doi: 10.1016/j.preghy.2021.05.007. Epub 2021 May 28.

Abstract

Preeclampsia (PE) is categorized as a pregnancy-related hypertensive disorder and is a serious concern in pregnancies. Several factors, including genetic factors (placenta gene expression, and imprinting), oxidative stress, the inaccurate immune response of the mother, and the environmental factors are responsible for PE development, but still, the exact mechanism of the pathogenesis has remained unknown. The main aim of the present study is to identify the gene expression signature in placenta tissue, to unveil disease etiology mechanisms. The GEO, PubMed, and ArrayExpress databases have selected to identify gene expression datasets on placenta samples of both preeclampsia and the normotensive controls. A comprehensive gene expression meta-analysis of fourteen publicly available microarray data of preeclampsia disease has performed to identify gene expression signature and responsible biological pathways and processes. Using two different meta-analysis pipeline (in-house and INMEX) we have identified a total of 1234 differentially expressed genes (DEGs) with in-house method, including 713 overexpressed and 356 under-expressed genes whereas 272 DEGs (131 over and 141 under-expressed) have identified with INMEX, across PEs and healthy controls. Comprehensive functional enrichment and pathway analysis was performed by EnrichR library, whic revealed "Asparagine N-linked glycosylation Homo sapiens", "Nef and signal transduction", "Hemostasis", and "immune system" among the most enriched terms. The present study sets out to explain a novel database of candidate genetic markers and biological pathways that play a critical role in PE development, which might aid in the identification of diagnostic, prognostic, and therapeutic informative molecules.

摘要

子痫前期 (PE) 被归类为与妊娠相关的高血压疾病,是妊娠中的一个严重问题。一些因素,包括遗传因素(胎盘基因表达和印迹)、氧化应激、母体免疫反应的不准确性以及环境因素,都与 PE 的发展有关,但发病机制的确切机制仍不清楚。本研究的主要目的是确定胎盘组织中的基因表达特征,以揭示疾病的发病机制。从 GEO、PubMed 和 ArrayExpress 数据库中选择了针对子痫前期和正常血压对照胎盘样本的基因表达数据集,以确定基因表达特征和负责的生物学途径和过程。对 14 个公开的子痫前期疾病微阵列数据集进行了综合基因表达荟萃分析,以确定基因表达特征和负责的生物学途径和过程。使用两种不同的荟萃分析管道(内部和 INMEX),我们确定了总共 1234 个差异表达基因(DEGs),其中 713 个上调和 356 个下调,而 INMEX 则识别出 272 个 DEGs(131 个上调和 141 个下调)。通过 EnrichR 库进行了全面的功能富集和途径分析,揭示了“人天冬酰胺 N-连接糖基化”、“Nef 和信号转导”、“止血”和“免疫系统”等最丰富的术语。本研究旨在解释一个新的候选遗传标记和生物学途径数据库,这些标记和途径在 PE 的发展中起着关键作用,这可能有助于识别诊断、预后和治疗有价值的分子。

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